BIOL4510 / KINE4510

BIOL4510KINE4510 Muscarinic Receptor and PI3Kinase Signaling Peter BackxParasympathetic Nervous SystemThe parasympathetic nervous system releases acetylcholine ACh which interacts with nicotinic ACh receptors at the ganglion and muscarinic ACh receptors at the target organs Muscarinic receptors were first identified by their selective activation by muscarine Muscarinic Receptors Muscarinic receptors are G protein coupled receptorsThere are five different muscarinic receptors M1M5 which are coupled to either G or G NOTE M1 M2 and M3 ioq11expressed in heart1 Acetylcholine slows heart rate The primary mechanism involved in decreased chronotropy is by the regulation of HCN channelsActivation of M2 receptors decreases cAMP levels which reduce HCN currents 10 nM ACh Higher concentrations of ACh activate acetylcholinesensitive K channels IK via either AchM2 or M3 receptorsThere are 80 times more M2 receptors than M3 receptors M3 are apparently only in atriaAcetylcholinesensitive K channels are heterotetrameric inward rectifying K channels comprised of two Kir31 and two Kir34 subunitsThese channels are highly expressed in sinoatrial nodal and atrial cells but are low or absent in ventricular myocytes 2